title: Chlamydia pneumoniae infection promotes vascular smooth muscle cell migration through a Toll-like receptor 2-related signaling pathway.
abstract: The migration of vascular smooth muscle cells (VSMCs) from the media to the intima is proposed to be a key event in the development of atherosclerosis. Recently, we reported that Chlamydia pneumoniae infection is involved in VSMC migration. However, the exact mechanisms for C. pneumoniae infection-induced VSMC migration are not yet well elucidated. In this study, we examined the role of the Toll-like receptor 2 (TLR2) activation-related signaling pathway in VSMC migration induced by C. pneumoniae infection. An Affymetrix-based gene expression array was conducted to identify the changes of gene expression in rat primary VSMCs (rVSMCs) infected with C. pneumoniae. Both the microarray analysis and quantitative real-time reverse transcription (RT)-PCR revealed that TLR2 mRNA expression was strongly upregulated 12 h after C. pneumoniae infection. RT-PCR and Western blot analysis further showed that the expression levels of TLR2 mRNA and protein significantly increased at the different time points after infection. Immunocytochemical analysis suggested a TLR2 recruitment to the vicinity of C. pneumoniae inclusions. Cell migration assays showed that the TLR2-neutralizing antibody could significantly inhibit C. pneumoniae infection-induced rVSMC migration. In addition, C. pneumoniae infection stimulated Akt phosphorylation at Ser 473, which was obviously suppressed by the PI3K inhibitor LY294002, thereby inhibiting rVSMC migration caused by C. pneumoniae infection. Furthermore, both the infection-induced Akt phosphorylation and rVSMC migration were suppressed by the TLR2-neutralizing antibody. Taken together, these data suggest that C. pneumoniae infection can promote VSMC migration possibly through the TLR2-related signaling pathway.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Tengteng
authors.initials: T
authors.lastname: Zhang
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wang
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.forename: Junyan
authors.initials: J
authors.lastname: Wei
authors.forename: Bingling
authors.initials: B
authors.lastname: Shen
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Zhelong
authors.initials: Z
authors.lastname: Xu
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D050197:Atherosclerosis / Q000378:metabolism; D002465:Cell Movement; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism*; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt